3-(2,2-dimethyl-3-hydroxypropyl)toluene

Endpoint summary

Description of key information

Acute oral toxicity: LD50 > 2000 mg/kg bw

Acute dermal toxicity: LD50 > 5000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1985-05-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

other: "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics", by the Staff of the Division of Pharmacology, FDA.

Version / remarks:

1959

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: not specified
- Weight at study initiation: 200-210 in average
- Fasting period before study: not specified
- Housing: single housing
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 2 °C
- Humidity: 50 - 60 %
- Air changes: not specified
- Photoperiod: 12 / 12 hrs dark / hrs light

Route of administration:

oral: gavage

Vehicle:

other: Tylose (CMC) + Tween 20

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 or 30 %
- Amount of vehicle: 1 to 1.7 mL/100 g bw, respectively

MAXIMUM DOSE VOLUME APPLIED: 1.7 mL / 100 g bw

Doses:

2; 3; 4; 5 mL/kg bw

recalculated with the relative density of 0.97 this corresponds to

1.94; 2.91; 3.76; 4.84 g/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: before administration and at day 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: Slope of the mortality curve: 1.24

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 3 460 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 14-d LD50

Mortality:

Mortality / treated animals

Males
2 mL/kg bw (1940 mg/kg bw): 0/5
3 mL/kg bw (2910 mg/kg bw): 1/5
4 mL/kg bw (3760 mg/kg bw): 1/5
5 mL/kg bw (4840 mg/kg bw): 5/5

Females
2 mL/kg bw (1940 mg/kg bw): 0/5
3 mL/kg bw (2910 mg/kg bw): 0/5
4 mL/kg bw (3760 mg/kg bw): 3/5
5 mL/kg bw (4840 mg/kg bw): 5/5

Clinical signs:

other: In all dose groups the preparation caused apathy, sedation, tremor, incoordination, abdominal ache symptoms, bloody nose-secretion and readiness for reflexing. The above mentioned symptoms continued up to 4 days or caused mortalities. Animals of the hi

Gross pathology:

Animals who died within 24 hours did not show any remarkable symptoms. The late mortalities of group III showed hyperaemia of the digestive tract. The same findings were observed in the surviving animals after 14 days in dosage group III.

Table 1 Mortalities for both sexes, aggregated

Dose Group	Dose level	24 h	7 days	14 days
I	2 mL/kg bw (1940 mg/kg bw)	0/10	0/10	0/10
II	3 mL/kg bw (2910 mg/kg bw)	0/10	1/10	1/10
III	4 mL/kg bw (3760 mg/kg bw)	1/10	4/10	4/10
IV	5 mL/kg bw (4840 mg/kg bw)	10/10	10/10	10/10

 

 

 

 

Table 2 Mean body weights males (g)

Dose Group	Dose level	Day 1	Day 14
I	2 mL/kg bw (1940 mg/kg bw)	205.2 ± 2.68	259.6 ± 6.88
II	3 mL/kg bw (2910 mg/kg bw)	204.8 ± 2.77	255.8 ± 5.38
III	4 mL/kg bw (3760 mg/kg bw)	205.2 ± 2.95	248.5 ± 5.74
IV	5 mL/kg bw (4840 mg/kg bw)	204.4 ± 2.70	-

 

Table 2 Mean body weight females (g)

Dose Group	Dose level	Day 1	Day 14
I	2 mL/kg bw (1940 mg/kg bw)	205.0 ± 2.35	220.2 ± 4.97
II	3 mL/kg bw (2910 mg/kg bw)	204.2 ± 2.39	217.6 ± 5.41
III	4 mL/kg bw (3760 mg/kg bw)	205.4 ± 2.19	216.0 ± 4.00
IV	5 mL/kg bw (4840 mg/kg bw)	204.0 ± 1.87	-

 

Interpretation of results:

GHS criteria not met

Conclusions:

Based on this acute oral toxicity study in the rat the LD50 was determined to be > 2000 mg/kg bw.

Executive summary:

The test item was assessed for its acute oral toxicity in the rat at dose levels of 2, 3, 4, and 5 mL/kg bw, respectively, as a dilution in Tylose (CMC) and Tween20. The LD50 after 24 h was determined to be 4.25 mL/kg bw. The 14 -days LD50 was 3.57 mL/kg bw. Clinical signs of toxicity were observed and included apathy, sedation, tremor, incoordination, abdominal ache symptoms, bloody nose-secretion and readiness for reflexing. Mortalities occurred within 24 h in the highest dose group. Later mortalities were observed in dose group II and III. Body weight development was decreased in a dose-related manner. Pathological examination revealed hyperaemia of the digestive tract.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

3 460 mg/kg bw

Quality of whole database:

GLP and guideline study.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987-05-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1981

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: not specified
- Weight at study initiation: males: 1.94 - 2.25 kg; females: 1.86 - 2.25 kg
- Fasting period before study: not specified
- Housing: single housing
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days at least

ENVIRONMENTAL CONDITIONS
- Temperature: 18 +/- 2 °C
- Humidity: 50 - 85 %
- Photoperiod: 12 / 12 hrs dark / hrs light

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- Type of wrap used: gauze pads, several wrappings of "Elastoplast" and "Stülpa"

REMOVAL OF TEST SUBSTANCE
- Washing: removal with wet disposable gauze
- Time after start of exposure: 24 h after administration

TEST MATERIAL
- Amount applied: 5 mL / kg bw
- Concentration: pure

Duration of exposure:

24 h

Doses:

5 mL / kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations, weighing on day 0, 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, skin alterations

Preliminary study:

Two female rabbits were employed in a preliminary range finding study. The dosage of the single dermal administration was 5.0 mL/kg. This preliminary study showed no mortalities.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 mL/kg bw

Remarks on result:

other: corresponding to 4985 mg/kg bw

Mortality:

Male: 5 mL/kg bw (ca. 4985 mg/kg bw); Number of animals: 5; Number of deaths: 0
Female: 5 mL/kg bw (ca. 4985 mg/kg bw); Number of animals: 5; Number of deaths: 0

Clinical signs:

other: None

Gross pathology:

Necropsies performed on all animals at termination exhibited no gross pathological findings.

Other findings:

Skin alterations:
The test item induced in all animals on the treated areas obvious erythema and edema. The symptoms described were observed in the same increased intensity during the first two days p.a. From the third day p. a. the symptoms diminished and from the 7th day p.a. 9 of 10 treated animals were without specific findings on the treated areas. One animal showed during the entire observation period fissures on the treated areas.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of this study, the acute dermal LD50 of the test item in the rabbit was determined to be greater than 5 mL/kg bw, corresponding to 4985 mg/kg bw.

Executive summary:

The acute dermal toxicity of the test item was investigated in two groups of 5 male and 5 female rabbits of the White New Zealand strain. Any signs of reaction were recorded during the 14-day observation period. On the treated areas the sample caused erythema and edemas. Post-dosing weight gains (2 week values) of all animals did not show essential differences. No mortalities were observed. Nothing abnormal was found in the animals necropsied on day 14. The determination of the dermal LD50 showed the following result:

24 h + 14 days

Male/female dermal LD50 > 5.0 mL/kg bw (corresponding to 4985 mg/kg bw)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Quality of whole database:

GLP and guideline study.

Additional information

Acute oral toxicity, rat, RL1

The test item was assessed for its acute oral toxicity in the rat at dose levels of 2, 3, 4, and 5 mL/kg bw, respectively, as a dilution in Tylose (CMC) and Tween20. The LD50 after 24 h was determined to be 4.25 mL/kg bw. The 14 -days LD50 was 3.57 mL/kg bw. Clinical signs of toxicity were observed and included apathy, sedation, tremor, incoordination, abdominal ache symptoms, bloody nose-secretion and readiness for reflexing. Mortalities occurred within 24 h in the highest dose group. Later mortalities were observed in dose group II and III. Body weight development was decreased in a dose-related manner. Pathological examination revealed hyperaemia of the digestive tract.

 

Acute dermal toxicity, rabbit, RL1

The acute dermal toxicity of the test item was investigated in two groups of 5 male and 5 female rabbits of the White New Zealand strain. Any signs of reaction were recorded during the 14-day observation period. The sample induced on the treated areas caused erythema and edemas. Post-dosing weight gains (2 week values) of all animals did not show essential differences. No mortalities were observed. Nothing abnormal was found in the animals necropsied on day 14. The etermination of the dermal LD50 showed the following result:

24 h + 14 days

Male/female dermal LD50 > 5.0 mL/kg bw (corresponding to 4985 mg/kg bw)

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute oral and dermal toxicity, the test item does not require classification according to Regulation (EC) No 1272/2008 (CLP), as amended for seventeenth time in Regulation (EU) No 2021/849.